Abstract

Kolka, Margaret A., and Lou A. Stephenson. Effect of luteal phase elevation in core temperature on forearm blood flow during exercise. J. Appl. Physiol. 82(4): 1079–1083, 1997.—Forearm blood flow (FBF) as an index of skin blood flow in the forearm was measured in five healthy women by venous occlusion plethysmography during leg exercise at 80% peak aerobic power and ambient temperature of 35°C (relative humidity 22%; dew-point temperature 10°C). Resting esophageal temperature (Tes) was 0.3 ± 0.1°C higher in the midluteal than in the early follicular phase of the menstrual cycle (P < 0.05). Resting FBF was not different between menstrual cycle phases. The Tes threshold for onset of skin vasodilation was higher (37.4 ± 0.2°C) in midluteal than in early follicular phase (37.0 ± 0.1°C;P < 0.05). The slope of the FBF to Tes relationship was not different between menstrual cycle phases (14.0 ± 4.2 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1for early follicular and 16.3 ± 3.2 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1for midluteal phase). Plateau FBF was higher during exercise in midluteal (14.6 ± 2.2 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1) compared with early follicular phase (10.9 ± 2.4 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1;P < 0.05). The attenuation of the increase in FBF to Tes occurred when Tes was 0.6°C higher and at higher FBF in midluteal than in early follicular experiments (P < 0.05). In summary, the FBF response is different during exercise in the two menstrual cycle phases studied. After the attenuation of the increase in FBF and while Tes was still increasing, the greater FBF in the midluteal phase may have been due to the effects of increased endogenous reproductive endocrines on the cutaneous vasculature.

body temperature regulation

the changing hormonal pattern during the human menstrual cycle may affect skin blood flow during exercise or heat stress, as it is well established that various estrogenic hormones influence vascular activity (1, 11, 28). In a “normal” menstrual cycle, circulating estradiol is elevated immediately before the luteinizing hormone “surge” preceding ovulation (late follicular phase) and, again, in the midluteal phase when progesterone is also increased (7, 9, 23). In a previous investigation (27), we described an increased esophageal temperature (Tes) for the onset of skin vasodilation during exercise in the midluteal phase of the menstrual cycle when both circulating progesterone and estradiol were elevated. Other laboratories have reported increased threshold for the onset of finger vasodilation during exercise (17) or increased threshold for cutaneous vasodilation during passive heating or cooling in the luteal phase of the menstrual cycle (13, 15, 16); the result being altered thermoregulatory control in the luteal phase associated with increased core temperature. These conclusions were supported by studies showing increased body temperature in humans after progesterone administration (2, 5, 23, 26), and in animals by decreased firing rate of preoptic warm-sensitive neurons and increased firing rate of preoptic cold-sensitive neurons after intravenous progesterone (24). These data support the hypothesis that there is an increased thermoregulatory set-point temperature during the midluteal phase of the menstrual cycle (3).

Forearm blood flow measurement provides an index of skin blood flow that is important in the assessment of thermoregulatory effector function (18, 20). As core temperature increases during exercise or heat stress, blood flow to the cutaneous vasculature increases proportionately. Exercise places limits on the cutaneous vasculature to dilate and, as core temperature approaches 38°C, skin blood flow levels off even as core temperature continues to increase (4, 18, 19,20). It is this relationship that was of interest in the present study.

The purpose of this study was to characterize possible differences in the skin blood flow responses in women during an exercise-heat stress in both the early follicular and midluteal phases of the menstrual cycle. We hypothesized that the leveling off of forearm blood flow would occur at different core temperatures in the two menstrual cycle phases studied. The approach (relatively intense exercise and heat) stimulated prolonged and fairly high cutaneous vasodilation, which allowed for the characterization of adaptive skin blood flow responses. The elevation in resting core temperature was the a priori criterion for the midluteal-phase experiments.

METHODS

Five healthy women completed two experiments each at an exercise intensity of 80% of peak aerobic power at 35°C (relative humidity 22%; dew-point temperature 10°C) after they were verbally apprised of the nature and risks of the study. The average age was 27.6 ± 4.4 (SD) yr, height was 1.68 ± 0.05 m, mass was 65.9 ± 7.0 kg, DuBois surface area was 1.75 ± 0.06 m2, and peak aerobic power was 2.87 ± 0.54 l/min. Exercise lasted 25–30 min.

Each volunteer had a normal menstrual cycle as defined by regular periodicity and was not taking oral contraceptives. To verify ovulatory menstrual cycles, daily basal body temperature (BBT; oral) was recorded by each subject on awakening. Data from an entire menstrual cycle were collected before inclusion in the study to determine whether BBT increased after ovulation (21). Higher BBT is closely correlated with higher plasma progesterone concentration in the luteal phase of the menstrual cycle (5). Consequently, elevated BBT in the luteal phase was an adequate post hoc method of determining that ovulation occurred and enabled us to schedule experiments in the appropriate menstrual cycle phase. From additional experiments in our laboratory and others, higher midluteal phase Tes readings occur when circulating estradiol and progesterone are elevated significantly, and Tes does not increase in the midluteal phase in the absence of elevated estradiol and progesterone (26). Testing in the midluteal phase was done on days when the resting core temperature was elevated (approximate days 19–22), consistent with elevated serum estradiol and progesterone (26). Testing in the early follicular phase was done on days 3–6 (day 1 = 1st day of menstrual flow).

Before testing, volunteers were thoroughly familiarized with all experimental techniques. On test days, preexperiment body weights were within 1% of the mean baseline body weight measured during preliminary testing to avoid dehydration. In all experiments, each subject sat in a chair positioned behind the cycle ergometer, such that during leg exercise the legs were parallel to the floor. The subject swallowed a catheter containing a thermocouple that was adjusted to approximate heart level based on 25% of each subject’s height. Surface thermocouples were placed at eight skin sites, one site being the forearm adjacent to the strain gauge, to estimate mean skin temperature (25). A mercury-in-Silastic strain gauge was placed on the forearm for the measurement of forearm blood flow by venous occlusion plethysmography (VOP; 10, 29). The strain gauge was placed around a section of forearm distal to the main mass of the muscles to decrease the proportion of muscle in the whole arm cylinder measured. The forearm was suspended by the wrist, with a sling apparatus anchored at two points, minimizing movement artifact during exercise as the arm and gauge moved in translation with the torso and the strain gauge position on the arm was near the height of the heart. During seated exercise, any increase in forearm blood flow is an accurate index of an increase in skin blood flow (18). Heart rate (HR) was measured from the electrocardiogram.

Temperatures and forearm blood flow were measured twice each minute. HR was recorded every 2.5 min, and metabolic heat production was estimated from oxygen utilization (open-circuit spirometry) at rest and during exercise. The Tes threshold for onset of cutaneous vasodilation and the slope of this relationship during exercise were determined by calculation of a linear-regression equation from the Tes and VOP data, when both parameters were increasing at the beginning of exercise (“a” on Figs. 1, 2, 3). In addition, the relationship of forearm blood flow and Tes, after the increase in forearm blood flow was attenuated during exercise, was also characterized by least squares regression (“b” and “c” on Figs.2, 3). Data from VOP and temperatures at rest, during exercise, and the Tes threshold for onset of cutaneous vasodilation were analyzed by analysis of variance procedures with repeated measures.

RESULTS

Resting Tes averaged 36.84 ± 0.21 (SD) °C in the early follicular phase experiments and 37.13 ± 0.23°C in the midluteal phase experiments (P < 0.05). Mean skin temperature averaged 35.87 ± 0.27°C in the early follicular phase experiments and 36.18 ± 0.27°C in the midluteal phase experiments (P < 0.05). There was no difference in forearm blood flow, HR, or metabolic rate at rest between the menstrual cycle phases studied. The Tes pattern (mean ± SD) is shown in Fig. 1 with the midluteal phase elevation in core temperature observed throughout exercise (P < 0.05). The forearm blood flow pattern (mean ± SD) is shown in Fig.2. There is a clear attenuation in the increase of forearm blood flow after 12–13 min of exercise in the early follicular phase and after 15 min in the midluteal phase, even as Tes continues to increase. Forearm blood flow was significantly higher during exercise after the plateau in the midluteal phase (14.6 ± 2.2 vs. 10.9 ± 2.4 ml ⋅ 100 ml−1 ⋅ min−1;P < 0.05).

The relationship of forearm blood flow, as an index of skin blood flow, to increasing Tes during the initial rapid rise of both variables (“a” in Figs. 1, 2, 3) indicated that the Tes threshold for onset of skin vasodilation during exercise averaged 37.0 ± 0.1°C in the early follicular phase and 37.4 ± 0.2°C in the midluteal phase (P < 0.05). The slope for the forearm blood flow to Tes relationship during the exercise transient averaged 14.0 ± 4.2 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1in early follicular experiments and 16.3 ± 3.2 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1in midluteal experiments. After this initial exercise transient, the relationship between forearm blood flow and Tes was attenuated as is the pattern for forearm blood flow (see Figs. 2 and3). This relationship between forearm blood flow and Tes is shown graphically in Fig. 3.

The relationship after the attenuation of the increase in forearm blood flow is presented in Table 1. The Tes at the attenuation of the forearm blood flow increase was higher in the midluteal experiments than in the early follicular experiments (P < 0.05). This attenuation of the increase in forearm blood flow occurred at a significantly higher skin blood flow in midluteal experiments than in early follicular experiments (P < 0.05). HR during the attenuation in forearm blood flow (“c” on Figs. 2 and 3) averaged 150 ± 11 beats/min in the early follicular phase experiments and 161 ± 9 beats/min in the midluteal phase experiments. Metabolic rate and mean skin temperature were not different during exercise in the two menstrual cycle phases studied.

Characteristics of skin blood flow and Tes at attenuation of the increase in FBF and Tes during high-intensity exercise

DISCUSSION

This study presents evidence that the “equilibrated” forearm blood flow (when the rapid increase in forearm blood flow is attenuated) is increased when the Tes is elevated during the midluteal phase of the menstrual cycle compared with the early follicular phase. Additionally, at any Tes >37.5°C, forearm blood flow is higher during exercise in the midluteal phase of the menstrual cycle compared with the early follicular phase of the menstrual cycle. The results also confirm previous work from our laboratory and others (13, 15, 16, 27) that increased resting core temperature during the midluteal phase affects, or is related to, a higher core temperature for the onset of skin vasodilation during exercise.

Forearm blood flow was 40–50% higher after the attenuated increase or equilibration during our luteal phase experiments. If there were a similarly increased blood flow extrapolated to the entire skin surface (assuming that cutaneous blood flow of other areas responds like the forearm), a significant increase in blood volume to the skin occurred. This redistribution would require increased cardiac output to maintain muscle perfusion during the high-intensity exercise as well as additional perfusion of the cutaneous circulation. No measurement of cardiac output was made during these experiments; however, HR was significantly increased in association with higher forearm blood flow during the luteal phase experiments, which may indirectly indicate higher cardiac output.

Evidence for reduced vasodilator activity as opposed to sympathetic restraint of skin blood flow has been presented (19, 20) to explain attenuation of the increase in skin blood flow. The current data indicate that forearm blood flow was significantly higher at the point of attenuation or equilibration during the midluteal phase experiments. It is not possible to determine from the current study whether this observation results from modulation of the vasodilatory, vasoconstrictor, or a combination of the two broad inputs to the cutaneous vasculature. It does show that forearm blood flow equilibration during an exercise-heat stress is different between menstrual cycle phases.

Little insight is provided from previous literature into the possible mechanisms for the increased forearm blood flow at the point of attenuation for a given Tes (Fig.3) observed in the present study. Previous conclusions (15-17, 27) were that the onset of vasodilation and cutaneous vasodilatory threshold temperature were altered between the early follicular and midluteal phases of the menstrual cycle in eumenorrheic women during exercise or heat stress. However, the finding that postural vasoconstriction was attenuated in the midluteal phase, compared with late follicular (preovulatory) and early follicular phase experiments (14), is consistent with the present study in that both responses could be explained by either increased vasodilatory signal(s), dampened vasoconstrictor signal(s), or a combination of both. In opposition, however, is the report that skin conductance, calculated from experiments conducted in a human calorimeter, was lower in the midluteal phase of the menstrual cycle compared with the follicular phase (12). It is difficult to compare the latter results (12) with the current experiments, as the follicular phase experiments were actually run during late follicular phase/preovulatory phase (day 9 ± 1) when the hormonal environment is characterized by high estrogen levels and low progesterone levels (7). In the present study, there was no significant difference in forearm blood flow between menstrual cycle phases when the subjects were resting in a warm environment (35°C).

The increased equilibrated forearm blood flow observed in women exercising in a hot environment during the midluteal phase in the present study is likely associated with changes in the reproductive endocrines characteristic of that menstrual cycle phase. Taken together with other data (19, 20), it is suggested that neuroendocrine, endocrine, or paracrine influences on the cutaneous vasculature that modulate vasodilatory and/or vasoconstrictor responses are activated by a signal resulting from the increased concentration of circulating 17β-estradiol and progesterone, which occurs in the midluteal phase. For example, 17β-estradiol has a vascular protective effect as it induces both prostacyclin and nitric oxide synthesis (8). This vascular protective effect is also apparent in postmenopausal women who receive hormone replacement therapy (11, 22). It is unknown whether progesterone plays any role in eliciting the increased equilibrated forearm blood flow in exercising eumenorrheic women during the midluteal phase, other than its proposed effect on the thermoregulatory set-point temperature (6, 15, 17, 27). Clearly, further studies are necessary to characterize the mechanisms altering cutaneous vasodilation during the midluteal phase in exercising women.

Acknowledgments

The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as official Department of the Army position, policy, or decision, unless so designated by other official documentation. Human subjects participated in these studies after giving their free and informed consent. Investigators adhered to Army Regulation 70–25 and United States Army Medical Research and Development Command Regulation 70–25 on the Use of Volunteers in Research.